Abstract:

In accordance with the present invention, a nutritional composition, a
method for enhancing the immune system development in an infant, and a
method for reducing allergic inflammatory responses in an infant are
provided. The nutritional composition comprises a protein source, a fat
source, a carbohydrate source, rumenic acid, DHA, and at least one
ganglioside. Both methods comprise administering to the infant a
combination of rumenic acid, DHA, and at least one ganglioside.

Claims:

2. The nutritional composition according to claim 1, wherein the amount of
rumenic acid is between about 0.01 to about 0.50 mg/g nutritional
composition.

3. The nutritional composition according to claim 1, wherein the amount of
DHA present is from about 2 mg/100 kilocalories to about 100 mg/100
kilocalories.

4. The nutritional composition according to claim 1, wherein the
gangliosides are present in an amount from about 5 to about 15 mg
lipid-bound sialic acid per liter nutritional composition.

5. The nutritional composition according to claim 1, wherein the
gangliosides are present in an amount from about 0.005 to about 0.1
weight percent of the total weight of the composition.

6. The nutritional composition according to claim 1, wherein the
ganglioside is selected from the group consisting of
monosialogangliosides, disialogangliosides, trisialogangliosides,
quadrasialogangliosides, pentasialogangliosides, and combinations
thereof.

8. The nutritional composition according to claim 1, wherein the
composition is an infant formula.

9. A method for enhancing immune system function in an infant comprising
administering a combination of rumenic acid, DHA, and at least one
ganglioside to the infant.

10. The method of claim 9 wherein the enhanced immune system function
comprises an improved resistance to infection.

11. The method of claim 9, wherein the amount of rumenic acid administered
to the infant is between about 50 mg to about 250 mg per day.

12. The method of claim 9, wherein the amount of DHA administered to the
infant is between about 2.5 mg/kg of body weight of the infant per day to
about 60 mg/kg of body weight of the infant per day.

13. The method of claim 9, wherein the amount of ganglioside administered
to an infant is between about 1 mg and 100 mg per day.

14. A method for reducing allergic inflammatory responses in an infant
comprising administering a combination of rumenic acid, DHA, and at least
one ganglioside to the infant.

15. The method according to claim 14 wherein the inflammatory response
being reduced is selected from the group consisting of asthma, wheezing,
atopic cough, bronchiolitis, bronchitis, and eczema.

16. The method of claim 14, wherein the amount of rumenic acid
administered to the infant is between about 50 mg to about 250 mg per
day.

17. The method of claim 14, wherein the amount of DHA administered to the
infant is between about 2.5 mg/kg of body weight of the infant per day to
about 60 mg/kg of body weight of the infant per day.

18. The method of claim 14, wherein the amount of ganglioside administered
to an infant is between about 1 mg and 100 mg per day.

19. A method for improving intestinal health in an infant comprising
administering a combination of rumenic acid, DHA, and at least one
ganglioside to the infant.

20. The method of claim 19 wherein the improvement in intestinal health is
selected from the group consisting of an improvement in mucin quality, an
improvement in mucin quantity, resistance to pathogenic bacterial
adherence in the intestinal wall, promotion of beneficial bacterial
adherence in the intestinal wall, and combinations thereof.

Description:

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS

[0001]This application claims the priority benefit of U.S. Provisional
Application No. 61/023,940 filed Jan. 28, 2008, which is incorporated by
reference herein in its entirety.

[0003]In an embodiment, the present invention is directed to an
nutritional composition comprising a protein source, a fat source, a
carbohydrate source, rumenic acid, DHA, and at least one ganglioside.

[0004]The nutritional composition of the invention may be useful in
enhancing immune system development and/or function in an infant by
administering a combination of ingredients comprising rumenic acid, DHA,
and at least one ganglioside to the infant.

[0005]The nutritional composition of the invention may also be useful in
reducing allergic inflammatory responses in an infant by administering a
combination of ingredients comprising rumenic acid, DHA, and at least one
ganglioside to the infant.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0006]Reference now will be made in detail to the embodiments of the
invention, one or more examples of which are set forth below. Each
example is provided by way of explanation of the invention, not a
limitation of the invention. In fact, it will be apparent to those
skilled in the art that various modifications and variations can be made
in the present invention without departing from the scope or spirit of
the invention. For instance, features illustrated or described as part of
one embodiment, can be used on another embodiment to yield a still
further embodiment.

[0007]Thus, it is intended that the present invention covers such
modifications and variations as come within the scope of the appended
claims and their equivalents. Other objects, features and aspects of the
present invention are disclosed in or are obvious from the following
detailed description. It is to be understood by one of ordinary skill in
the art that the present discussion is a description of exemplary
embodiments only, and is not intended as limiting the broader aspects of
the present invention.

[0008]The present invention is directed, in an embodiment, to an
nutritional composition comprising a protein source, a fat source, a
carbohydrate source, rumenic acid, DHA, and at least one ganglioside.

[0009]Rumenic acid is a conjugated linoleic acid (CLA) found in the fat of
ruminants and in dairy products. It is an omega-7 trans fat and its lipid
shorthand name is cis-9, trans-11 18:2 acid. Its chemical formula is
C18H32O2 and its structure is shown below:

##STR00001##

[0010]Of the individual isomers of CLA, rumenic acid has been implicated
as the most biologically active. It is the predominant isomer
incorporated into the phospholipids of cell membranes, liver
phospholipids, and triglycerides. It is also the predominant dietary form
of CLA, obtained from fats derived from human milk, ruminant animals,
including milk, dairy products, and meat. In fact, in fat from ruminant
meats and dairy products, rumenic acid is present as approximately 80% to
90% of the total CLA.

[0011]In an embodiment of the invention, rumenic acid is present in an
amount ranging from about 0.01 to about 0.50 mg/g nutritional
composition. In another embodiment of the invention, rumenic acid is
present in an amount ranging from about 0.02 to about 0.30 mg/g
nutritional composition.

[0012]If the composition of the invention is administered to an infant or
child, an amount of rumenic acid ranging from about 50 mg to about 250 mg
per day may be administered. In another embodiment, the amount of rumenic
acid administered to an infant or child may range from about 50 mg to
about 100 mg per day. In yet another embodiment, the amount of rumenic
acid administered to an infant or child may range from about 60 mg to
about 80 mg per day.

[0013]In certain embodiments, the invention contemplates the use of CLA
and CLA derivatives as sources of rumenic acid. For example, if CLA is
used as the source of rumenic acid, it may be free, bound through ester
linkages, or provided in the form of an oil containing CLA triglycerides.
If CLA triglycerides are utilized, the triglycerides may be partially or
wholly comprised of CLA attached to a glycerol backbone. The CLA may also
be provided as a methylester or ethylester. Furthermore, the CLA may be
used in the form of a non-toxic salt, such as a potassium or sodium salt.

[0014]In another embodiment, the invention contemplates the use of
vaccenic acid (11-trans-octadecenoic acid) as a source of rumenic acid,
Vaccenic acid is a major trans fatty acid in milk fat and is a major
precursor of CLA in milk fat. Desaturation of vaccenic acid to rumenic
acid is catalyzed by Δ9-desaturase in humans. Turpeinen, et
al., Bioconversion of Vaccenic Acid to Conjugated Linoleic Acid in
Humans, Am. J. Clin. Nutr. 76: 504-510 (2002).

[0015]The nutritional composition of the invention also comprises DHA. DHA
is a long chain polyunsaturated fatty acid (LCPUFA) found in high
concentrations in the infant brain and retina. Sastry, P. S., Lipids of
Nervous Tissue: Composition and Metabolism, Progress Lipid Res. 24:69-176
(1985); Fliesler, S. J., et al. Chemistry and Metabolism of Lipids in the
Vertebrate Retina, Progress Lipid Res. 22:79-131 (1983). Chemically, DHA
is a carboxylic acid with a 22-carbon chain and six cis double bonds,
with the first double bond being located at the third carbon from the
omega end. Thus, DHA is often referred to as an omega-three (ω-3)
fatty acid. DHA is derived from the parent essential fatty acid
α-linolenic acid through alternate desaturation and elongation.

[0016]The amount of DHA in the present invention may be from about 2
mg/100 kilocalories (kcal) to about 100 mg/100 kcal. In another
embodiment, the amount of DHA may be from about 5 mg/100 kcal to about 75
mg/100 kcal. In yet another embodiment, the amount of DHA may be from
about 15 mg/100 kcal to about 60 mg/100 kcal.

[0017]Some embodiments of the invention encompass the administration of
the composition to an infant or child. In this embodiment, an infant may
be between the age of birth and 1 year. In some embodiments, a child may
be between the ages of about 1 year and 12 years. In some embodiments,
the child may be between the ages of about 4 and 9 years.

[0018]If DHA is administered to an infant or child, the amount of DHA may
be between about 2.5 mg/kg of body weight/day and about 60 mg/kg of body
weight/day. In another embodiment, the amount of DHA administered may be
between about 6 mg/kg of body weight/day and about 40 mg/kg of body
weight/day. In yet another embodiment, the amount of DHA administered may
be between about 12 mg/kg body weight/day and about 30 mg/kg body
weight/day. In a still further embodiment, the amount of DHA administered
may be between about 18 mg/kg of body weight/day and about 24 mg/kg of
body weight/day.

[0019]The source of the DHA can be any source known in the art such as
marine oil, fish oil, single cell oil, egg yolk lipid, brain lipid, and
the like. In particular embodiments, the DHA may be sourced from the
single cell Martek oil, DHASCO®, or variations thereof. The DHA can
be in natural form, provided that it does not result in any substantial
deleterious effect on the infant. Alternatively, the DHA can be used in
refined form.

[0020]The nutritional composition also comprises at least one ganglioside.
Gangliosides are compounds composed of glycosphingolipids with one or
more sialic acid moieties (n-acetylneuraminic acid) linked on the sugar
chain. They consist of a hydrophobic ceramide moiety and a hydrophilic
oligosaccharide chain. Ceramide is a chimera of a sphingoid base and a
fatty acid joined with an amide bond. The oligosaccharide chain is linked
to the sphingoid base. Gangliosides are part of the membrane fraction of
the milk fat globule, which derives from the apical plasma membrane of
the secretory cells in the lactating mammary gland.

[0021]In an embodiment, the nutritional composition of the invention
comprises at least one ganglioside. In this embodiment, the ganglioside
may be selected from those known in the art that would be compatible with
the other components of the invention. In an embodiment, the ganglioside
is selected from the group consisting of monosialogangliosides,
disialogangliosides, trisialogangliosides, quadrasialogangliosides,
pentasialogangliosides, and combinations thereof.

[0022]Gangliosides are commonly defined by a short-hand nomenclature
system in which "G" refers to a ganglioside, "M", "D", "T" "Q", and "P"
refer to mono-, di-, tri-, quadra- and pentasialogangliosides,
respectively, and the subscript numbers 1, 2, 3, etc. refer to the order
of migration of the gangliosides on thin-layer chromatography. The
subscripts "a", "b" and "c" indicate the series of conversion by
glycosyltransferases and sialyltransferases into more complex
gangliosides.

[0023]The ganglioside of the invention may be any ganglioside that is
compatible with the other components of the invention. In some
embodiments, the ganglioside is selected from the group consisting of
GM3, GM2, GM1, GD3, GD2, GD1a, GD1b,
GT3, GT2, GT1, GT1b, GQ1b, GP1, and
combinations thereof. In other embodiments, the gangliosides comprise
GM1, GD1a, GD1b, GT1b, and GQ1b.

[0024]In a particular embodiment of the invention, the gangliosides
comprise GD3 and GM3. In this embodiment, GD3 may comprise
between about 20% and 40% of the total gangliosides and GM3 may
comprise about 20% and 40% of the total gangliosides. In another
embodiment, GD3 may comprise about 30% of the total gangliosides and
GM3 may comprise about 30% of the total gangliosides.

[0025]In yet another embodiment of the invention, the gangliosides
comprise GM3 and GD3. In this embodiment, the GM3
gangliosides may have a major fatty acid composition of 22:0, 18:0, 16:0,
and 24:0. Similarly, the GD3 gangliosides may have a major fatty
acid composition of 18:0, 16:0, 19:0 and 22:0. In an embodiment, between
about 30% and 60% of the fatty acids on the gangliosides of the present
invention have a chain length of 20 or more carbon atoms. In another
embodiment, between about 35% and 50% of the fatty acids on the
gangliosides of the present invention have a chain length of 20 or more
carbon atoms. In a particular embodiment, the fatty acids of the
gangliosides of the present invention are selected from the group
consisting of long chain polyunsaturated fatty acids, ofeic acid, fatty
acids with 16 or fewer carbon atoms, and combinations thereof.

[0026]In an embodiment of the invention, the gangliosides are present in
an amount of about 5 to 15 mg lipid-bound sialic acid (LBSA) per liter
nutritional composition. In an embodiment of the invention, the
gangliosides are present in an amount of about 7 to 12 mg LBSA per liter
nutritional composition. In another embodiment, the gangliosides are
present in an amount of about 9 to 10 mg LBSA per liter nutritional
composition.

[0027]In an embodiment of the invention, the gangliosides are present in
an amount which comprises about 0.005 to about 0.1 weight percent of the
total weight of the composition. In another embodiment of the invention,
the gangliosides are present in an amount which comprises about 0.01 to
about 0.05 weight percent of the total weight of the composition.

[0028]For an infant or child, an amount of ganglioside ranging from about
1 mg to about 100 mg per day may be administered. In another embodiment,
the amount of ganglioside administered to an infant or child may range
from about 10 mg to about 50 mg per day.

[0029]In an embodiment, the nutritional composition can be an infant
formula, a human milk supplement, a baby food, a baby cereal, a follow-on
formula, or a children's nutritional product. As used herein, the term
"infant formula" means a composition that satisfies the nutrient
requirements of an infant by being a substitute for human milk. In a
particular embodiment, the nutritional composition, infant formula, human
milk supplement, or children's nutritional product is in a powdered form.
In other embodiments, the nutritional composition, infant formula, human
milk supplement, or children's nutritional product may be in a liquid or
ready-to-use form.

[0030]In an embodiment, the infant formula for use in the present
invention is nutritionally complete and contains suitable types and
amounts of lipid, carbohydrate, protein, vitamins and minerals. The
amount of lipid or fat typically can vary from about 3 to about 7 g/100
kcal. The amount of protein typically can vary from about 1 to about 5
g/100 kcal. The amount of carbohydrate typically can vary from about 8 to
about 12 g/100 kcal. Protein sources can be any used in the art, e.g.,
nonfat milk, whey protein, casein, soy protein, hydrolyzed protein, amino
acids, and the like. Carbohydrate sources can be any used in the art,
e.g., lactose, glucose, corn syrup solids, maltodextrins, sucrose,
starch, rice syrup solids, and the like. Lipid sources can be any used in
the art, e.g., vegetable oils such as palm oil, canola oil, corn oil,
soybean oil, palmolein, coconut oil, medium chain triglyceride oil, high
oleic sunflower oil, high oleic safflower oil, and the like.

[0031]Conveniently, commercially available infant formula can be used. For
example, Enfalac, Enfamil®, Enfamil® Premature Formula,
Enfamil® with Iron, Enfamil® LIPIL®, Lactofree®,
Nutramigen®, Pregestimil®, and ProSobee® (available from Mead
Johnson & Company, Evansville, Ind., U.S.A.) may be supplemented with
suitable levels of rumenic acid, DHA, and at least one ganglioside and
used in practice of the invention.

[0032]In some embodiments of the invention, the nutritional composition
contains additional components which may include probiotics, prebiotics,
or additional long chain polyunsaturated fatty acids (LCPUFAs). The term
"probiotic" means a microorganism that exerts beneficial effects on the
health of the host. Any probiotic known in the art may be added, provided
it is suitable for combination with the other components of the
supplement. For example, the probiotic may be chosen from the group
consisting of Lactobacillus and Bifidobacterium. Alternatively, the
probiotic can be Lactobacillus rhamnosus GG.

[0033]In certain embodiments, the nutritional supplement of the present
invention additionally comprises at least one prebiotic. The term
"prebiotic", as used herein, means a non-digestible food ingredient that
stimulates the growth and/or activity of probiotics. In this embodiment,
any prebiotic known in the art may be added, provided it is suitable for
combination with the other components of the supplement. In a particular
embodiment, the prebiotic can be selected from the group consisting of
polydextrose, fructo-oligosaccharide, gluco-oligosaccharide,
galacto-oligosaccharide, inulin, isomalto-oligosaccharide,
xylo-oligosaccharide and lactulose.

[0034]In yet another embodiment of the invention, additional LCPUFAs may
be supplemented into the nutritional composition. In this embodiment, the
LCPUFA may comprise arachidonic acid (ARA). If used, the amount of ARA in
the present invention may be from about 4 mg/100 kilocalories (kcal) to
about 100 mg/100 kcal. In another embodiment, the amount of ARA may be
from about 10 mg/100 kcal to about 67 mg/100 kcal. In yet another
embodiment, the amount of ARA may be from about 20 mg/100 kcal to about
50 mg/100 kcal. In a particular embodiment, the amount of ARA may be from
about 25 mg/100 kcal to about 40 mg/100 kcal. In one embodiment, the
amount of ARA is about 30 mg/100 kcal.

[0035]The LCPUFA source may or may not contain eicosapentaenoic acid
(EPA). In some embodiments, the LCPUFA used in the invention contains
little or no EPA. For example, in certain embodiments that the infant
formulas used herein contain less than about 20 mg/100 kcal EPA; in some
embodiments less than about 10 mg/100 kcal EPA; in other embodiments less
than about 5 mg/100 kcal EPA; and in still other embodiments
substantially no EPA.

[0036]In a particular embodiment, the combination of rumenic acid, DHA,
and at least one ganglioside provides an improvement in intestinal
health. It is believed that the combination of these components may
provide an improvement in both mucin quality and quantity, resist
pathogenic bacterial adherence and promote beneficial bacterial adherence
within the intestinal wall. Thus, it is believed that the combination of
rumenic acid, DHA, and at least one ganglioside has a beneficial overall
impact on intestinal health.

[0037]In some embodiments, the combination of rumenic acid, DHA, and at
least one ganglioside aids in immune system development and/or function
in mammals. For example, the combination of rumenic acid, DHA, and at
least one ganglioside may enhance resistance to infection and/or reduce
allergic inflammatory responses including, but not limited to asthma,
wheezing, atopic cough, bronchiolitis, bronchitis, and eczema. Thus, in
an embodiment, the invention is directed to a method for enhancing the
immune response in an infant comprising administering a combination of
rumenic acid, DHA, and at least one ganglioside to the infant. In another
embodiment, the invention is directed to a method for enhancing
resistance to infection in an infant comprising administering a
combination of rumenic acid, DHA, and at least one ganglioside to the
infant. In yet another embodiment, the invention is directed to a method
for reducing allergic inflammatory responses in an infant comprising
administering a combination of rumenic acid, DHA, and at least one
ganglioside to the infant.

[0038]In certain embodiments, the combination of rumenic acid, DHA, and at
least one ganglioside provides immune system enhancement and/or reduction
of allergic inflammatory responses. It is believed that the activity of
the combination of rumenic acid, DHA, and at least one ganglioside is
greater than the added activity expected when each of these three
compounds are administered separately.

[0039]In particular embodiments, the subject is "in need" of the
composition of the invention. For example, a subject may be in need
because he is immunocompromised, chronically ill, or is a premature
infant. Thus, in one embodiment of the invention, the composition is
administered to subjects in need of such treatment.

[0040]All references cited in this specification, including without
limitation, all papers, publications, patents, patent applications,
presentations, texts, reports, manuscripts, brochures, books, internet
postings, journal articles, periodicals, and the like, are hereby
incorporated by reference into this specification in their entireties.
The discussion of the references herein is intended merely to summarize
the assertions made by their authors and no admission is made that any
reference constitutes prior art. Applicants reserve the right to
challenge the accuracy and pertinence of the cited references.

[0041]These and other modifications and variations to the present
invention may be practiced by those of ordinary skill in the art, without
departing from the spirit and scope of the present invention, which is
more particularly set forth in the appended claims. In addition, it
should be understood that aspects of the various embodiments may be
interchanged in whole or in part. Furthermore, those of ordinary skill in
the art will appreciate that the foregoing description is by way of
example only, and is not intended to limit the invention so further
described in such appended claims. Therefore, the spirit and scope of the
appended claims should not be limited to the description of the preferred
versions contained therein.